Treatment of Children With Cerebral Palsy With Autologous Umbilical Cord Blood, a Pilot Study

This study is a phase II, prospective, double blind, placebo-controlled study of the efficacy of autologous umbilical cord blood infusion.

The study population will consist of 72 children ages 2 months to 12 years with cerebral palsy. The population will be randomly assigned to 2 groups, 36 children in each group. The study group be treated by cord blood in the beginning of the study and the control group by placebo product. The study population will be stratified to reduce variance 3 groups by age: 2-12 months / 1-6 years / 6-12 years The study will consist of 4 stages Stage 1: initial assessment by physiotherapist and occupational therapist / treatment by cord blood or placebo / blood work before and after treatment Stage 2: at stage 1 + 3 months assessment by physiotherapist and occupational therapist Stage 3: at stage 1 + 6 months assessment by physiotherapist and occupational therapist / cross-over treatment by cord blood or placebo / blood work before and after treatment Stage 4: at stage 1 + 12 months assessment by physiotherapist and occupational therapist The primary outcome is improvement motor skills six months after treatment at stage 3

Study Overview

• Status: Recruiting
• Conditions: Cerebral Palsy
• Intervention / Treatment: Other: Autologous umbilical cord blood transfusion; Other: placebo

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Omer Bar-Yosef, MD.PHD; Phone Number: 972-35302895; Email: Omer.BarYosef@sheba.health.gov.il

Study Locations

• Israel
  • Ramat Gan, Israel
    • Recruiting
    • Chaim Seba Medical Center
    • Contact: Omer Bar-Yosef

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 2 month and ≤ 12 years.

• Performance status for children older than 2 months and younger than 12 months including all the following (Gross Motor Function Classification Score is less indicative before 12 months):

  • Abnormal General Movements (in infants 2-6 months)
  • Abnormal Hammersmith Infant Neurological Examination

• Performance status for children older than 12 months

  • Bilateral spastic cerebral palsy (diplegia or quadraplegia): Gross Motor Function Classification Score levels I - IV
  • Spastic hemiplegia: Gross Motor Function Classification Score levels I - IV. A subject classified as GMFCS level I with significant upper extremity impairment will be eligible if the affected upper extremity is used as an assist only.
  • Bilateral hypotonic cerebral palsy (diplegia or quadraplegia): Gross Motor Function Classification Score levels I - IV.
• An abnormal brain MRI suggestive of an acquired etiology (and not genetic etiology or brain malformation).
• 4. Autologous umbilical cord blood available at a private or public cord blood bank with a minimum total nucleated cell dose of ≥ 2 x 10e7 cells/kilogram.
• 5. Parental consent.

Exclusion Criteria:

• Autism and autistic spectrum disorders without motor disability.
• Hypsarrhythmia.
• Intractable seizures causing epileptic encephalopathy.
• Evidence of a progressive neurologic disease.
• Known HIV or uncontrolled bacterial, fungal, or viral infections.
• Impaired renal or liver function as determined by serum creatinine >1.5mg/dL and/or total bilirubin >1.3mg/dL.
• Head circumference >3 standard deviations below the mean for age.
• Known genetic disease or phenotypic evidence of a genetic disease on physical examination.
• Requires ventilatory support, including home ventilator
• Surgical procedure or botulinum toxin injection from 6 months prior to the study and during the time of the study
• Patient's medical condition does not permit safe travel.

• Previously received any form of cellular therapy.

  • Autologous umbilical cord blood unit has any of the following:
  • Total nuclear cell dose < 2 x 10e7 cells/kilogram
  • Positive maternal infectious disease markers (except CMV)
  • Evidence of infectious contamination of the cord blood unit
• Lack of a test sample to confirm identity
• Evidence of a genetic disease
• Unable to obtain parental consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: group 1	Other: Autologous umbilical cord blood transfusion; single dose of an autologous umbilical cord blood transfusion
Placebo Comparator: group 2	Other: placebo; The placebo product will consist of the standard ingredients of the acellular content of the UCB unit. It will consist of 20 ml Dextran (Plander 40.000 - 50g/500ml, solution for infusion) and 20 ml of human Albumin 5% (solution for infusion). The volume of placebo product will be 40 ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motor developmental improvement	Gross Motor Function Measurement - 66 (GMFM-66). All score are normalized with mean 100 and STD of 15. High score is better than low score .	6 months
Motor developmental improvement	Peabody developmental motor scales-second edition (PDMS-2). All score are normalized with mean 100 and STD 10. High score is better	6 months
Functional assessment	Pediatric Evaluation of Disability Evaluation . Score 0-100 higher score better functionality Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional assessment	Adaptive Behavior Assessment System, Third Edition (ABAS-3). All score are normalized with mean 100 and STD of 10. High score is better than low score .	6 months
Functional assessment	Vineland Adaptive Behavior Scales-Second Edition (VINELAND-II). All score are normalized with mean 100 and STD of 15. High score is better than low score .	6 months

Collaborators and Investigators

• Sponsor: Sheba Medical Center
• Investigators: Study Director: Omer Bar-Yosef, MD.PHD, Sheba Medical Center

Publications and helpful links

General Publications

• Bax M, Goldstein M, Rosenbaum P, Leviton A, Paneth N, Dan B, Jacobsson B, Damiano D; Executive Committee for the Definition of Cerebral Palsy. Proposed definition and classification of cerebral palsy, April 2005. Dev Med Child Neurol. 2005 Aug;47(8):571-6. doi: 10.1017/s001216220500112x.
• Colver A, Fairhurst C, Pharoah PO. Cerebral palsy. Lancet. 2014 Apr 5;383(9924):1240-9. doi: 10.1016/S0140-6736(13)61835-8. Epub 2013 Nov 20.
• Clark SL, Hankins GD. Temporal and demographic trends in cerebral palsy--fact and fiction. Am J Obstet Gynecol. 2003 Mar;188(3):628-33. doi: 10.1067/mob.2003.204.

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2020
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: January 15, 2020
• First Submitted That Met QC Criteria: January 25, 2020
• First Posted (Actual): January 28, 2020

Study Record Updates

• Last Update Posted (Actual): January 20, 2021
• Last Update Submitted That Met QC Criteria: January 17, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: cerebral palsy, autologous umbilical cord blood
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Brain Damage, Chronic; Cerebral Palsy; Paralysis
• Other Study ID Numbers: SHEBA-18-5102-OBY-CTIL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: data set of the baseline of the children, the quantity of cord blood transfusion they received and the clinical followup information.
• IPD Sharing Time Frame: within 2 years from the end of data collection
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No